In response to national efforts to develop, improve and deliver vaccines, Emory University requests P-20 grant support for an Exploratory Center for Interdisciplinary Research in Vaccinology (ECIRVE). Vaccines are the most cost-effective prevention known, but the introduction and use of vaccines has become increasingly slowed by a series of obstacles, including delays in identification of candidate antigens for vaccines, incomplete understanding of human immune correlates of protection, limited understanding of the predisposition to vaccine failures or adverse events, difficulty with immune response in the very young, the very old and immunocompromised, incomplete definition of the best strategies for the design of infectious and non-infectious disease vaccines, problems with use and acceptance of vaccines, and problems with vaccine supply and financing. The goals of this application are to develop a comprehensive program to better integrate new quantitative methodologies into vaccinology and to engage multidisciplinary science (genetics, bioinformatics, microbiology and human immunology, biostatistics and analytical epidemiology, behavioral research, economics, population biology, clinical medicine and engineering) in solving significant and complex problems in vaccine development, safety and adverse events, production and supply, acceptance and use. Emory has made an exceptional commitment to vaccine research and has attracted or developed national leaders in basic vaccine sciences (immunology and molecular pathogenesis), vaccine development, vaccine trials, vaccine modeling, vaccine epidemiology and vaccine policy. In the activities of this grant, this outstanding expertise will be combined with key leaders and centers in genetics, bioinformatics, behavioral sciences, economics, engineering, and population biology to plan new solutions to vaccine problems. The first aim will create a multidisciplinary scientific working council of national leaders and center directors to develop novel strategies for problem-solving in vaccinology. The second specific aim will explore how to integrate new quantitative methodologies (genomics, proteomics, systems biology and other computational methodologies) for assessment of vaccine immune responses and reactogenicity, develop better dynamic methods for modeling of vaccine use, and plan integrative models for economic assessment of vaccines. The specific aims will be accomplished through a strong leadership structure, bi-weekly meetings of the multidisciplinary scientific council, yearly workshops; external advisory committee input; and two linked pilot feasibility projects to 1) explore the design and limitations of quantitative methodologies to define molecular signatures of adaptive and innate immune responses to influenza vaccines, and 2) design novel approaches to influenza vaccine policy.